Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = −0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

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Effects of a D-Xylose Preload With or Without Sitagliptin on Gastric Emptying, Glucagon-Like Peptide-1, and Postprandial Glycemia in Type 2 Diabetes

Diabetes Care ◽

10.2337/dc12-2294 ◽

2013 ◽

Vol 36 (7) ◽

pp. 1913-1918 ◽

Cited By ~ 35

Author(s):

T. Wu ◽

M. J. Bound ◽

B. R. Zhao ◽

S. D. Standfield ◽

M. Bellon ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Emptying ◽

Postprandial Glycemia ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

Clinical Science ◽

10.1042/cs0950719 ◽

1998 ◽

Vol 95 (6) ◽

pp. 719-724 ◽

Cited By ~ 34

Author(s):

C. Mark B. EDWARDS ◽

Jeannie F. TODD ◽

Mohammad A. GHATEI ◽

Stephen R. BLOOM

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Plasma Glucose ◽

Healthy Subjects ◽

Therapeutic Potential ◽

Double Blind ◽

Gut Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

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